Viewpoint on the Brain Disorder in Autism

  (based on a review of research papers in the medical literature)

Viewpoint on the brain disorder(2003) (View in 2000)

The auditory system The inferior colliculus Hemoglobin & the brain

Concepts of autism Autism spectrum Social responsibility

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Conrad Simon Memorial Research Initiative
http://conradsimon.org /inc/docinfo.shtml
Date posted:  January 20, 2023 06:44 PM
© Copyright 2003
Eileen Nicole Simon
Introduction | I. Brain damage at birth | II. Auditory system | III. Language
IV.  Childhood handicaps | V. Brainstem Damage | VI. References | Summaries
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Topics (section links):

Introduction

I. BRAIN DAMAGE AT BIRTH
1 - Asphyxia at Birth
2 - Hypoxic Birth
3 - Asphyxia Versus Hypoxia
4 - Human Conditions
5 - Stages of Asphyxia
6 - The Umbilical Cord Lifeline
7 - Developmental Delay
8 - Poor Manual Dexterity
9 - Progressive Degeneration
10 - Autism and Complications at Birth
11 - Mercury, and Other Toxic Factors

II. THE AUDITORY SYSTEM
12 - Metabolic Rank Order
13 - The Auditory System
14 - Auditory Dysfunction

III. LANGUAGE
15 - Language by Ear
16 - Verbal Auditory Agnosia
17 - Echolalic Speech
18 - Echolalic Speech is Pragmatic

IV. CHILDHOOD HANDICAPS
19 - Auditory and Motor Handicaps
20 - Increased Incidence of Autism
21 - Fetal to Postnatal Adaptation
22 - Forgotten History
23 - Worth Remembering
24 - Hemoglobin
25 - Infant Anemia
26 - Autism in Twins
27 - Male-Female Differences

V. BRAINSTEM DAMAGE
28 - Variable Vulnerability
29 - Patterns of Damage
30 - Wernicke's Encephalopathy
31 - Suffocation at the Molecular Level
32 - Thiamine Deficiency
33 - Brain-Gut Relationship

VI. REFERENCES
34 - Bibliography
35 - Autism and Complications at Birth
36 - Umbilical Cord Clamping

Summaries

[Site Links]


Overview (References):

The following references are grouped according to a wide range of subjects. My first priority was to understand brain mechanisms underlying language and how children learn to speak. Conrad was born pale and flaccid and did not cry for several minutes after birth. Nevertheless his development was normal, and he began speaking early – his older brother was his best friend and teacher! Conrad's nursery school teacher advised us to have him seen by a psychiatrist because of his echolalic manner of speaking, and the diagnosis was autism. No child fit Kanner's description of autism better than Conrad.

William Windle's article describing damage of the inferior colliculi by asphyxia at birth was the starting point, in 1969, for my personal quest to understand mechanisms by which language circuits in the brain can be damaged. The brain, not genes on chromosomes, is the most reasonable place to look for the cause of autism. The brain and how it is affected by all etiologies of autism should be the focus of research on autism.


. . . .

[Top]

VI. REFERENCES

34 - Bibliography

Asphyxia and Hypoxia at Birth
  1. Windle, W. F. (1969). Brain damage by asphyxia at birth. Scientific American, 221(#4), 76-84.
  2. Myers RE (1972) Two patterns of perinatal brain damage and their conditions of occurrence. American Journal of Obstetrics and Gynecology 112:246-276.

    Cerebral Blood Flow
  3. Landau WM, Freygang WH, Rowland LP, Sokoloff L, Kety SS (1955) The local circulation of the living brain; values in the unanesthetized and anesthetized cat. Transactions of the American Neurological Association 80:125-129.
  4. Kety SS (1962) Regional neurochemistry and its application to brain function. In French, JD, ed, Frontiers in Brain Research. New York: Columbia University Press, pp 97-120.
  5. Reivich M, Jehle J, Sokoloff L, Kety SS (1969) Measurement of regional cerebral blood flow with antipyrine-14C in awake cats. Journal Of Applied Physiology 27:296-300.
  6. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo-14-C-antipyrine. American Journal of Physiology, 234, H59-H66.

    Measures of Aerobic Metabolism (Deoxyglucose Uptake)
  7. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. Journal of Neurochemistry 28:897-916.
  8. Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Gallagher B, Hoffman E, Alavi A, Sokoloff L (1977) Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-d-glucose. Acta Neurologica Scandinavica. Supplementum 64:190-1

    Correlates of High Deoxyglucose Uptake
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    Research on Blood Flow and Glucose Uptake
  15. Sokoloff L (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. Journal of Cerebral Blood Flow and Metabolism 1:7-36.
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    Early Research of Windle and Coworkers
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    Circulatory Arrest in Adult Monkeyts
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    Developmental Degeneration Following Asphyxia
  30. Faro MD & Windle WF (1969) Transneuronal degeneration in brains of monkeys asphyxiated at birth. Experimental Neurology 24:38-53.

    Biochemistry of Respiration
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    Brainstem Lesions in Human Infants
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    Minimal Cerebral Dysfunction?
  44. Windle WF (1969) Asphyxial brain damage at birth, with reference to the minimally affected child. In Perinatal Factors Affecting Humn Development. Pan American Health Organization, proc. spec. session, 8th meeting, pp. 215-221
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    Umbilical Cord Clamping
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    Bilirubin Only Gets into Oxygen-Deprived Tissues
  54. Lucey JF, Hibbard E, Behrman RE, Esquival FO, Windle WF (1964) Kernicterus in asphyxiated newborn monkeys. Experimental Neurology 9:43-58.

    Stages of Drowning
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    Low 5-minute Apgar Score
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    Historical Textbooks on Obstetrics
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    Sound Localization
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    Large Handwriting (Macrographia)
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    Neurotrophic Influences on Maturation
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    Brain Abnormalities in Autism
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    Autism and Complications at Birth
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    Cephalhematoma
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    Controversy Over Mercury Preservatives in Vaccines
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    Mercury Damages the Auditory System
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    Fluoro-deoxyglucose Brain Scans
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    Cardiac Arrest Encephalopathy
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    Importance of the Auditory System
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    General Awareness and Consciousness
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    Fast Acting Anesthesia
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    Kanner's Original Description
  123. Kanner L (1943) Autistic disturbances of affective contact. Nervous Child 2:217-250.

    Auditory Evoked Potentials
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    Disruption of Mitochondrial Function
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  279. Graf WD, Marin-Garcia J, Gao HG, Pizzo S, Naviaux RK, Markusic D, Barshop BA,Courchesne E, Haas RH (2000) Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. J Child Neurol. 2000 Jun;15(6):357-61.
  280. Fillano JJ, Goldenthal MJ, Rhodes CH, Marin-Garcia J (2002) Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol. 2002 Jun;17(6):435-9.

    Thiamine Deficiency
  281. Peters RA (1936) The biochemical lesion in vitamin B1 deficiency. Lancet, May 23, 1161-1165.
  282. Williams RR (1961) Toward the Conquest of Beriberi. Cambridge, MA: Harvard University Press.
  283. Dreyfus PM, Victor M (1961) Effects of thiamine deficiency on the central nervous system. American Journal of Clinical Nutrition 9: 414-425.
  284. Carpenter KJ (2000) Beriberi, White Rice, and Vitamin B: A Disease, a Cause, and a Cure. Berkeley: University of California Press.

    Thiamine Treatment
  285. Lonsdale D, Shamberger RJ, Audhya T. (2002) Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: A pilot study. Neuroendocrinology Letters 23:303-308.

    Thiamine Deficiency in Total Parenteral Nutrition
  286. Vortmeyer AO, Hagel C, Laas R (1992) Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition. Journal of Neurology, Neurosurgery and Psychiatry 55:826-829.
  287. Hahn JS, Berquist W, Alcorn DM, Chamberlain L, Bass D. Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage. Pediatrics. 1998 Jan;101(1):E10.

    Thiamine Deficiency in Animals
  288. Evans CA, Carlson WE, Green EG (1942) The pathology of Chastek paralysis in foxes. A counterpart of Wernicke's hemorrhagic polioencephalitis of man. American Journal of Pathology 18:79-90.
  289. Rinehart JF, Friedman M, Greenberg LD (1949) Effect of experimental thiamine deficiency on the nervous system of the rhesus monkey. Archives of Pathology 48:129-139.
  290. Jubb KV Saunders LZ, Coates HV (1956) Thiamine deficiency encephalopathy in cats. Journal of Comparative Pathology 66:217-227.
  291. Witt ED, Goldman-Rakic PS (1983) Intermittent thiamine deficiency in the rhesus monkey. I. Progression of neurological signs and neuroanatomical lesions. Annals of Neurology 13:376-395.

    Brainstem Control of Autonomic Functions
  292. Johnson RH, Eisenhofer G, Lambie DG. The effects of acute and chronic ingestion of ethanol on the autonomic nervous system. Drug Alcohol Depend. 1986 Dec;18(4):319-28.

    Wernicke's Encephalopathy in Gastrointestinal Disorders
  293. Korsakoff SS (1889) Psychic disorder in conjunction with multiple neuritis. Translated by Victor M & Yakovlev PI (1955) Korsakoff's psychic disorder in conjunction with peripheral neuritis: a translation of Korsakoff's original article with brief comments on the author and his contribution to clinical medicine, Neurology 5:394-405.
  294. Neubürger K (1937) Wernickesche Krankheit bei chronischer Gastritis. Ein Beitrag zu den Beziehungen zwischen Magen und Gehirn. Zeitschrift für die gesamte Neurologie und Psychiatrie 160:208-225.
  295. Albers JW, Nostrant TT, Riggs JE. Neurologic manifestations of gastrointestinal disease. Neurol Clin. 1989 Aug;7(3):525-48.
  296. Butterworth RF. Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. Metab Brain Dis. 1995 Mar;10(1):1-8.
  297. Kril JJ. Neuropathology of thiamine deficiency disorders. Metab Brain Dis. 1996 Mar;11(1):9-17.
  298. Holzer P, Michl T, Danzer M, Jocic M, Schicho R, Lippe IT. Surveillance of the gastrointestinal mucosa by sensory neurons. J Physiol Pharmacol 2001 Dec;52(4 Pt 1):505-21.

    Hypovolemic Shock at Birth
  299. Morley GM (2003) Neonatal Resuscitation: Life that Failed. http://www.obgyn.net/pb/pb.asp?page=/pb/articles/neonatal-resuscitation
  300. Hankins GD, Koen S, Gei AF, Lopez SM, Van Hook JW, Anderson GD (2002) Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstetrics and gynecology 99:688-91.

35 – Autism and Complications at Birth


  • "… 5 items were found to significantly predict group membership (prescriptions taken during pregnancy, length of labor, viral infection, abnormal presentation at delivery, and low birth weight)."
    Wilkerson DS, Volpe AG, Dean RS, Titus JB. Perinatal complications as predictors of infantile autism. Int J Neurosci. 2002 Sep;112(9):1085-98.

  • "Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results:The risk of autism was associated with daily smoking in early pregnancy (OR = 1.4; CI = 1.1-1.8), maternal birth outside Europe and North America (OR = 3.0; CI = 1.7-5.2), cesarean delivery (OR = 1.6; CI = 1.1-2.3), being small for gestational age (SGA; OR = 2.1; CI = 1.1-3.9), a 5-minute Apgar score below 7 (OR = 3.2, CI = 1.2-8.2), and congenital malformations (OR = 1.8, CI = 1.1-3.1)." Note: The OR and CI were both greatest for 5-min Apgar score below 7.
    Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. 2002 Jul;13(4):417-23.

  • "Children with autism spectrum disorders have lower optimality (higher rates of complications) than unaffected siblings…"
    Zwaigenbaum L, Szatmari P, Jones MB, Bryson SE, MacLean JE, Mahoney WJ, Bartolucci G, Tuff L. Pregnancy and birth complications in autism and liability to the broader autism phenotype. J Am Acad Child Adolesc Psychiatry 2002 May;41(5):572-9

  • "In a sample of families selected because each had exactly two affected sibs, we observed a remarkably high proportion of affected twin pairs, both MZ and DZ…"
    Greenberg DA, Hodge SE, Sowinski J, Nicoll D. Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet 2001 Nov;69(5):1062-7

  • "The highest OR [odds ratio] was found for vaginal breech delivery (OR 6.7), birth weights above 5 kg (OR 6.3), and second born twins (OR 4.1)."
    Thorngren-Jerneck K, Herbst A. Low 5-minute Apgar score: A population-based register study of 1 million term births. Obstet Gynecol 2001;98:65-70

  • "Among the children with a serious medical condition, 34.4% also had ante- or perinatal antecedents. Among the 33% without any medical factor, 77% also had ante- or perinatal antecedents."
    Bodier C, Lenoir P, Malvy J, Barthélemy C, Wiss M, Sauvage D. (2001) Autisme et pathologies associées. Étude clinique de 295 cas de troubles envahissants du developpment. [Autism and associated pathologies. Clinical study of 295 cases involving development disorders] Presse Médicale 2001 Sep 1; 30(24 Pt 1):1199-203.

  • "… specific complications that carried the highest risk of autism and PDD-NOS represented various forms of pathologic processes with no presently apparent unifying feature."
    Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics. 2001 Apr;107(4):E63.

  • "AD was identified in 18 of the 5,271 children and the incidence was 34 per 10,000 (0.34%). This value was more than twice the highest prevalence value previously reported in Japan. Children with AD had a significantly higher history of the meconium aspiration syndrome (p = .0010) than the controls. Autistic patients had different risk factors than CP." Note: CP (cerebral palsy) occurred in 57 of the 5,271 children.
    Matsuishi T, Yamashita Y, Ohtani Y, Ornitz E, Kuriya N, Murakami Y, Fukuda S, Hashimoto T, Yamashita F. Brief report: incidence of and risk factors for autistic disorder in neonatal intensive care unit survivors. J Autism Dev Disord. 1999 Apr;29(2):161-6

  • "…[obstetric] optimality score (OS), were compared in two groups: 78 families containing an autistic proband (ICD-10 criteria) and 27 families containing a down syndrome (DS) proband… RESULTS: Autistic and DS probands had a significantly elevated OS compared with unaffected siblings, regardless of birth order position. The elevation was mainly due to an increase in mild as opposed to severe obstetric adversities."
    Bolton PF, Murphy M, Macdonald H, Whitlock B, Pickles A, Rutter M. Obstetric complications in autism: consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):272-81

  • "Males with AS showed a trend toward lower Apgar scores at one minute …"
    Ghaziuddin M, Shakal J, Tsai L. Obstetric factors in Asperger syndrome: comparison with high-functioning autism. J Intellect Disabil Res. 1995 Dec;39 ( Pt 6):538-43.

  • "These data provide slight support for the contribution of nonspecific pre- and perinatal factors to other etiological bases of autism."
    Lord C, Mulloy C, Wendelboe M, Schopler E. Pre- and perinatal factors in high-functioning females and males with autism. J Autism Dev Disord. 1991 Jun;21(2):197-209.

  • In most of the pairs discordant for autism, the autistic twin had more perinatal stress.
    Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry. 1989 May;30(3):405-16.

  • "Abnormal presentation at birth is the only factor that occurred more frequently for the autistic sample…"
    Levy S, Zoltak B, Saelens T. A comparison of obstetrical records of autistic and nonautistic referrals for psychoeducational evaluations. J Autism Dev Disord. 1988 Dec;18(4):573-81.

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36 - Umbilical Cord Clamping

Clamping the umbilical cord at birth is a human invention. The umbilical cord is an infant's lifeline throughout gestation; it should go without saying that it remains the newborn's lifeline until lung function is established. Clamping the cord before a baby breathes can be expected to result in at least a brief period of oxygen deprivation.

Looking back at historical textbooks on obstetrics, waiting at least for the infant to breathe on its own was traditionally always required before cutting the cord [58-65].

From 1850 to 1930:
  • "A strong healthy child, as soon as it is born, will begin to breathe freely, and in most cases cry vigorously. As soon as it has thus given satisfactory proof of its respiratory power, you may at once proceed to separate it from its mother by tying and dividing the umbilical cord."
    Swayne JG (1856) Obstetric Aphorisms: For the use of students commencing midwifery practice. London: John Churchill, p 20.
  • "As soon as the child cries we may proceed to tie and separate the cord."
    Playfair WS (1880) A Treatise on the Science and Practice of Midwifery. Philadelphia: Henry C. Lea, p 283
  • "The cord should not be tied until the child has breathed vigorously a few times. When there is no occasion for haste, it is safer to wait until the pulsations of the cord have ceased altogether."
    Lusk WT (1882) The Science and Art of Midwifery. New York: D Appleton and Company, pp 214-215
  • "Immediately after its birth the child usually makes an inspiratory movement and then begins to cry. In such circumstances it should be placed between the patient's legs in such a manner to have the cord lax, and thus avoid traction upon it… Normally the cord should not be ligated until it has ceased to pulsate…"
    Williams JW (1917) Obstetrics: A Text-Book for the Use of Students and Practicioners, Fourth Edition. New York & London: D. Appleton and Company, pp 342-343
  • "As soon as the lungs begin to function, the circulation through the umbilical arteries normally ceases in from five to fifteen minutes after birth."
    Williams JW (1930) Obstetrics: A Text-Book for the Use of Students and Practicioners, Sixth Edition. New York: D. Appleton-Century, pp 418-419

By the 1940s a change of opinion is evident:

  • "We have adopted an intermediate course, feeling that to always wait for complete cessation of pulsation frequently interferes with the proper conduct of the third stage of labor, and at the same time, that most of the available blood in the cord had been incorporated in the fetal circulation during the few minutes immediately following delivery."
    Stander HJ (1941) Williams Obstetrics, Eighth Edition. New York, London: D. Appleton-Century company, pp 429-430.

  • "Whenever possible, clamping or ligating the umbilical cord should be deferred until its pulsations wane or, at least, for one or two minutes…
    There has been a tendency of late, for a number of reasons, to ignore this precept. In the first place the widespread use of analgesic drugs in labor has resulted in a number of infants whose respiratory efforts are sluggish at birth and whom the obstetrician wishes to turn over immediately to an assistant for aspiration of mucus, and if necessary, resuscitation. This readily leads to the habit of clamping all cords promptly."

    Eastman HJ (1950) Williams Obstetrics, Tenth Edition. New York: Appleton-Century-Crofts , pp 397-398

Would Williams recognize the 20th edition of his textbook?

  • "Although the theoretical risk of circulatory overloading from gross hypervolemia is formidable, especially in preterm and growth-retarded infants, addition of placental blood to the otherwise normal infant's circulation ordinarily does not cause difficulty… Our policy is to clamp the cord after first thoroughly clearing the infant's airway, all of which usually takes about 30 seconds."
    Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC, Hankins GDV, Clark SL, Williams JW, (1997) Williams Obstetrics, Twentieth Edition. Stamford, Conn: Appleton & Lange, pp 336-337.


Preventing jaundice

  • It appears that Saigal et al (1972) and Saigal & Usher (1977) may have initiated the fear that delayed clamping of the umbilical cord could result in circulatory overload, polycythemia (too many red blood cells) and jaundice. But polycythemia is more often a physiological response to abnormalities like methemoglobinemia, which results from a genetic or drug-induced abnormality of the hemoglobin molecule.

    Saigal S, O'Neill A, Surainder Y, Chua LB, Usher R. Placental transfusion and hyperbilirubinemia in the premature. Pediatrics. 1972 Mar;49(3):406-19.

    Saigal S, Usher RH. Symptomatic neonatal plethora. Biol Neonate. 1977;32(1-2):62-72.

  • Jellett (1910) in a Manual of Midwifery discussed the issue of polycythemia after stating, "The old dispute as to when the cord should be tied possesses now little more than an academic interest, as it is conclusively settled that this should not be done until all pulsations in the cord have ceased."

    Jellett cited research apparently well known in 1910: White (1785, 1773) had written about the absurdity of supposing that it was possible for the change from placental to pulmonary circulation, with all that this implies, to take place in a moment, "that this wonderful alteration in the human machine should be brought about in one instant of time, and at the will of a bystander?"

    Jellett further cited research by Schmidt (1894) in which it was found that 72 percent of children in whom immediate ligation of the cord was done were jaundiced, while only 42 percent were jaundiced when the cord was not tied until ten minutes after birth. It may be time to consider whether postnatal anemia isn't a greater risk for more infants than polycythemia and jaundice.

    Jellett H (1910) A Manual of Midwifery for Students and Practitioners. New York: William Wood & Company.

    White C (1773) A Treatise on the Management of Pregnant and Lying-In Women. Science History Publications/ Watson Publishing International, Canton MA, 1987.


A Radical Change

Whatever its motivation, the now routine clamping of the umbilical cord within 30 seconds following birth is a radical change from traditional practice. If an infant is breathing on its own at the time of cord clamping, the most important transition from fetal to neonatal life has taken place (see Mercer & Skovgaard, 2002). This transition has not taken place in an infant in need of resuscitation. It may be only a small minority of infants who do not breathe immediately at birth, but might this minority account for the increased prevalence of autism or other developmental disabilities?

Mercer JS, Skovgaard RL. Neonatal transitional physiology: a new paradigm. J Perinat Neonatal Nurs. 2002 Mar;15(4):56-75.
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January 20, 2023 06:44 PM

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